wcsbeau at superior.carleton.ca (OPIRG) writes:
>...
This long article, seriously edited down here, provided some Q&A with
previous posters and a summary of an article on the potential damaging
effects of food additives containing excitatory amino acids. The
references are peer reviewed work for the most part. I don't have a
particular axe to grind on either side of this issue -- I'm interested
but more interested in Olney's data than in his beliefs, and those who
read this original post will recall that many sentences began, Olney
believes...
I want to point out some major stoppers in this text that gave me pause
as I read it. I've not read all the literature cited here, but the
literature on excitotoxic amino acids is huge, and I've read a fair amount of
it and have used excitotoxics such as kainic acid and ibotenic acid
in my research.
I am glad to see literate pieces such as this on the net. My compliments
to the author.
>The major areas of excitotoxic action are the arcuate nucleus of
>the hypothalamus, and the neurohypophysis (median eminence (ME)).
Not exactly. These area *some* major areas. Domoic acid damages *all*
CVO's, for instance. Even MSG damages the subfornical organ and organum
vasculosum laminae terminalis as well as others named here.
>tate. And Madeline Price was adamant when I spoke with her a few
>weeks back, that aspartic acid can easily pass both the gut wall,
>and the placenta. So spiking *can* occur, according to some medi-
>cal researchers.
It is amazing how many scientists who were adamant on the floor
of the convention become not so certain once they see their names
cited in print without permission as a personal communication in a
classy publication. That's not the case here, but hard core scientists
learn quickly to trust only the part of what a person says that has
passed peer review. For all I know, she was citing peer reviewed
work -- that should have been cited instead or in addition.
>I'm afraid I'm going to have to disagree with you on that: Olney
>and others have clearly shown that acute spiking can cause severe
>necrosis in the arcuate and the ME, within hours of exposure, in
>fetal brain, as well as neonatal brain tissue. Check out Olney
>(1988), see attached.
Here as in other places in the text experiments are referred
to as if the neonatal brain of the rat or mouse implied something about
all neonatal brains. This is a break from what I perceive is a good
appreciation for individual and species differences elsewhere in the piece.
In truth, the neonatal rat or mouse brain is nothing at all like the neonatal
human brain. The rodents are born prematurely, even to the point that they
undergo their brain growth spurt *after* birth. The blood-brain barrier is
not complete in the neonatal rodent. Thus, injected excitotoxins have
especially easy access to the brain and can do massive damage to CVO's and
even to nuclei that are within the barrier in adults. In humans, the brain
growth spurt happens during the third trimester of pregnancy, and the
child is born with a reasonably well-formed barrier. One should thus
exercise extreme caution when drawing inferences about humans based on the
rodent developmental literature, especially during the neonatal stage.
>The major affected areas are CVO's - circumventricular organs, and they
>are not in areas involved in cognition. The damaged areas govern
>neuroendocrine functioning. Other effected areas include the visual
>system in developing brain.
True enough in animals developmentally mature enough to have a complete
blood-brain barrier.
>%% edited version of paper on excitotoxic
>%% food additives follows
As with the rest, severely edited:
>*****************************************************************************
>NEUROTOXIC FOOD ADDITIVES: A Call for Caution
>Copyright, C. Dianne Murray, 1992
......
>Excitatory neurotransmitters are necessary to life, yet, in large
>doses, they are toxic. Excitotoxicity occurs when an substantial
>excess of an excitatory compound (e.g. Glu or Asp), or an excito-
>toxin (e.g. domoic acid), is available to post-synaptic mem-
>branes, causing too rapid and frequent depolarization and firing
>of a neuron, and its subsequent death (Olney, 1988). Excitotox-
To fill in the gap: the cell probably dies because so much electrolyte
enters the cell during this frenetic excitatory activity that water
is drawn osmotically inside the cell until it bursts like an
overfilled water balloon. These amino acids are useful as research tools
because discrete brain injections cause localized death of cell bodies,
but not of fibers of passage, within the sphere of the injection site.
Thus, the lesion can determine that the effects of localized damage
by other sorts of lesions, such as electrolytic or radio frequency lesions,
occurred because of cell bodies within the area rather than axons
traversing the distance between remote nuclei.
>The blood-brain barrier protects the brain from the effects of
>most toxins circulating in the blood (Olney, 1988) but excitotox-
>ins circumvent this protective system; they act on some of the
>circumventricular organs (CVO's), areas which lie outside the
>blood-brain barrier, specifically the median eminence and the ar-
>cuate nucleus of the hypothalamus, the pituitary gland, and the
>area postrema (Olney, 1988).
In 14 years and 5 grants studying CVOs I've never heard the arcuate
nucleus called a CVO. Median eminence, yes. The only CVO that I know
of that has a blood-brain barrier is the subcommissural organ.
I don't have Olney's 1988 paper -- what was the source he used to
determine that the arcuate nucleus was a CVO? Was it supposed to
lack a blood-brain barrier? If he truly determined this I would be
very interested (and surprised!).
>Different species exhibit different
>susceptibilities to Glu and Asp.; humans are the most sensitive
>tested (Olney, 1984, 1988)). Sensitivity depends, in part, on ex-
>posure, and exposure on uptake across the gut wall. Humans' are
>very sensitive because they have the most efficient gut uptake
>for these compounds; high levels of circulating excitotoxins are
>thus quickly achieved after consumption. (Olney, 1988). Individu-
>als show differences in susceptibility to excitotoxins.
Once again we need to be very careful drawing inferences about the
susceptibilities involved: the thrust of this argument has to do mainly
with neonatal, or at least young, rodents and children. The
different species show different susceptibilities, but so also do
different developmental ages. Despite the assertion above, then,
the neonatal rodent should be more susceptible (not less)
because of the aforementioned differences in developmental age at the time
of birth -- More immature GI system, brain, brain barrier system, etc.
Thus:
>Glu and Asp cause neuron death in developing animals. Age is
>negatively correlated with sensitivity to excitotoxins in the
>diet, thus fetuses and infants are most at risk. Olney (1988)
>found effects within 4 hrs. of oral MSG administration in infant
>mice. The effects of oral and subcutaneous doses of Glu and MSG
>to infants are summarized in Table 1. Similar effects would be
>expected for Aspartame, since Aspartame is 50% Asp, and Asp expo-
>sure has been shown to cause similar neurological damage, mainly
>in the arcuate nucleus of the hypothalamus (ANH), the median em-
>inence region (ME), and the anterior pituitary (Olney, 1988).
**** omitted table of references to infant rodent studies ***
The reader who has dauntlessly followed this far will recognize that
the infant mice studies just referred to have nothing to say about
infant humans. They *may* say something about human fetuses, but
comparing a baby mouse given an oral or SC injection of MSG with a
human fetus receiving varying blood levels across a placenta, if it gets
in at all, is a difficult exercise. Keep in mind also that the
repeated statement about Asp damaging the AN, ME, and anterior pit was done
in rodents, not in humans. Comparing effective doses is very difficult.
>MSG destroys dopaminergic and cholinergic systems in the ANH-ME
>region. The lateral median eminance is especially effected (Daw-
>son, Simpkins, and Wallace, 1989). Single acute subcutaneous ad-
>ministrations of MSG to developing mice have been shown to des-
>troy substantial portions of the arcuate and pituitary (Burde,
>Schainker, and Kayes, 1971; Olney, 1970). Olney, Labruyere, and
>de Gubareff (1980) obtained similar results for voluntary oral
>doses of MSG and Aspartame to infant mice.
I'm not familiar with these particular studies, and there's not enough
information here to analyze them: many studies of excitotoxics use
them for the explicit purpose of producing lesions in CVOs to examine the
effects of CVO damage as the animals grow to adulthood. This gives
one kind of information on the function of CVOs. They use the neonatal rat
because it is actually *difficult* to produce damage in adults, even
at very high doses. Because of the different developmental ages, these
studies say little about humans. The voluntary oral dose of MSG and
Aspartame is interesting. However, the dose involved would be
crucial. Was this nothing but Diet Sprite? If so (concentrationwise,
that is) it is impressive. If the dose was much larger, however, it
would have less relevance. The fact that it is "voluntary oral" consumption
means little. Infant rats have enormous tolerances for foul tastes,
strangely enough. For instance, they readily drink salty solutions at
a concentration that would make a grown rat gag (actually, the accepted
scientific term for this in the taste reactivity literature is, "make a
yukky face"). Who knows about MSG or Aspartame.
*******
Thanks for citing so much empirical data.
Sorry I was not more familiar with these particular studies but
time is precious and it's mi